While highly active anti-retroviral therapy (HAART) can suppress HIV-1 replication, treatment currently does not eradicate infection or prevent a low level of continued replication. The major objective of this project is directed to defining the anatomic and cellular compartments in which HIV-1 is produced and persists before and during HAART, and from which infection re-emerges on discontinuation of HAART.
The Specific Aim of the project is to identify, characterize and quantify cellular sources of virus production and persistence in gutassociated lymphatic tissues (GALT) and peripheral lymphatic tissues (LTs), using state-of-the-art in situ Technologies of in situ hybridization, in situ PCR, immunohistochemistry and quantitative image analysis, with the long-term goal of capitalizing on the new insights into HIV-1 reservoirs generated by this analysis to design even more effective treatments.
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|Rothenberger, Meghan K; Keele, Brandon F; Wietgrefe, Stephen W et al. (2015) Large number of rebounding/founder HIV variants emerge from multifocal infection in lymphatic tissues after treatment interruption. Proc Natl Acad Sci U S A 112:E1126-34|
|Winchester, Lee C; Podany, Anthony T; Baldwin, Joshua S et al. (2015) Determination of the rifamycin antibiotics rifabutin, rifampin, rifapentine and their major metabolites in human plasma via simultaneous extraction coupled with LC/MS/MS. J Pharm Biomed Anal 104:55-61|
|Cory, Theodore J; Winchester, Lee C; Robbins, Brian L et al. (2015) A rapid spin through oil results in higher cell-associated concentrations of antiretrovirals compared with conventional cell washing. Bioanalysis 7:1447-55|
|Sanchez, Joyce L; Hunt, Peter W; Reilly, Cavan S et al. (2015) Lymphoid fibrosis occurs in long-term nonprogressors and persists with antiretroviral therapy but may be reversible with curative interventions. J Infect Dis 211:1068-75|
|Mitchell, Caroline; Roemer, Emily; Nkwopara, Evangelyn et al. (2014) Correlation between plasma, intracellular, and cervical tissue levels of raltegravir at steady-state dosing in healthy women. Antimicrob Agents Chemother 58:3360-5|
|Rizzardi, Anthony E; Rosener, Nikolaus K; Koopmeiners, Joseph S et al. (2014) Evaluation of protein biomarkers of prostate cancer aggressiveness. BMC Cancer 14:244|
|Podany, Anthony T; Winchester, Lee C; Robbins, Brian L et al. (2014) Quantification of cell-associated atazanavir, darunavir, lopinavir, ritonavir, and efavirenz concentrations in human mononuclear cell extracts. Antimicrob Agents Chemother 58:2866-70|
|Fletcher, Courtney V; Staskus, Kathryn; Wietgrefe, Stephen W et al. (2014) Persistent HIV-1 replication is associated with lower antiretroviral drug concentrations in lymphatic tissues. Proc Natl Acad Sci U S A 111:2307-12|
|Rizzardi, Anthony E; Vogel, Rachel Isaksson; Koopmeiners, Joseph S et al. (2014) Elevated hyaluronan and hyaluronan-mediated motility receptor are associated with biochemical failure in patients with intermediate-grade prostate tumors. Cancer 120:1800-9|
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